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Cancer immunotherapy has emerged as a revolutionary tool to target malignant cells changing the paradigm for cancer treatment and providing potential curative outcomes for subsets of patients. Investigators from the Immunotherapy Institute of the BIDMC Cancer Center have played pivotal roles in advancing many of the central areas of this field in both the basic science and translational arenas.
Cancer Vaccine Program
BIDMC’s Cancer Vaccine Program is one of the largest cancer vaccine and cellular immunotherapy programs throughout the world. Immunotherapy Institute Co-Director Dr. David Avigan, Deputy Director Jacalyn Rosenblatt and colleagues developed a personalized, patient-specific vaccine created from the patients’ own tumors hybridized with potent immune stimulatory cells, dendritic cells. A broad array of self and neo-antigens are presented in the context of dendritic cell mediated co-stimulation.
In phase I/II clinical trials of patients with blood cancers, vaccination results in the potent expansion of tumor specific T cells in the blood and bone marrow. Notably, vaccination-induced disease regression and protection from relapse in patients with multiple myeloma and acute leukemia, respectively.
Based on these encouraging data, the fusion vaccine was chosen to be the first cellular immunotherapy to be studied in a multicenter cooperative group study. The national transplant study for myeloma is a first-of-its-kind collaborative effort to examine the immunologic and clinical impact of cellular therapy. Led by BIDMC, the study involves leaders in the field of cancer immunotherapy from across the US. Furthermore, this multicenter trial offers a unique platform to fully understand myeloma-specific immunity and correlate these findings with clinical outcomes.
BIDMC has played a central role in developing immune checkpoint blockade agents as highly effective therapy for solid tumors and blood cancers. These studies have revolutionized the approach to cancer therapy.
Dr. David McDermott, Immunotherapy Institute Co-Director, with translational investigators Drs. Jim Mier and Rupul Bhatt, have been involved in the development and conduct of critical trials. The trials demonstrated that blockade of the PD1/PDL1 pathway results in immune activation and disease regression in patients with advanced malignancies including melanoma, renal and lung cancer.
In addition, the studies have demonstrated synergy with combination therapy using agents that block different checkpoint pathways. As a part of the National Cancer Institute-supported Renal Spore grant led by Dr. McDermott, the team is attempting to develop biomarkers that predict patient response to checkpoint blockade. They are also pursuing the integration of these approaches with other therapies.
Defining Novel Targets and Immunoregulatory Pathways
A team of scientists led by Dr. Cox Terhorst at BIDMC have defined SLAMF7 and related proteins on Chronic Leukocytic Leukemia cells as novel targets for antibody and cellular immunotherapy. In collaboration with the RNA Institute, the Slack, and Avigan laboratories are examining the role of noncoding RNAs in modulating the immunosuppressive milieu of the tumor microenvironment. This role includes expression of negative costimulatory factors and myeloid suppressor cells.